title: A nuclear factor that binds to ras-responsive enhancer elements is present in human tumor cells.
abstract: The ras protein can be viewed as molecular switches for undetermined signal transduction pathways. We are interested in defining the downstream effectors and targets associated with ras signal transduction. A nuclear target of ras action is the conserved sequence element TGACTCT, which functions as a ras-responsive transcriptional element (RRE). An Mr 120,000 nuclear factor present in transformed murine cells recognizes the RRE. Mutation of the conserved RRE element to the palindromic element AGACTCT created a binding site that is recognized with 5-fold greater affinity by the Mr 120,000 factor. The palindromic element functions as an RRE as determined by transient transfection assays. UV-crosslinking of nuclear factors in human tumor cell lines to the palindromic element revealed that an Mr 120,000 factor that recognized RREs was present in cells that contain activated Ha- or N-ras genes, but not in human tumor cells that lack activated ras. Expression of exogenous activated ras in a human tumor cell line that lacks the oncogene induced the Mr 120,000 factor. The Mr 120,000 factor, which we have termed ras-responsive factor 1, is an intermediate in the signal transduction pathway that links ras to the nucleus and may play a role in the initiation or progression of human tumors containing an activated ras gene.
authors.affiliation: Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: R D
authors.initials: RD
authors.lastname: Owen
authors.forename: M C
authors.initials: MC
authors.lastname: Ostrowski
mesh_terms: D001483:Base Sequence; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000032:analysis*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016296:Mutagenesis; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins / Q000032:analysis*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D008156:Luciferases